The goal of the proposed research is to elucidate the molecular mechanisms whereby an excitable cell exerts a trophic influence on another excitable cell. The work will be carried out in tissue culture using cloned lines of nerve and muscle cells. Trophic effects will be monitored using a variety of probes. Purified neurotoxin and anti-acetylcholine receptor antibody will be used to investigate the mechanisms whereby a nerve cell regulates the synthesis, and distribution on the limiting cell membrane, of acetylcholine receptors in the nerve or muscle being innervated. Various animal and microbial toxins, specific antisera, and several enzyme activities will be used to detect and investigate trophic interactions between nerve and muscle and between nerve and nerve. The interaction of excitable cells in tissue culture will be investigated with emphasis on cell specificity and molecular mechanisms involved. The investigation of molecular mechanisms will center on the role of membrane-membrane interaction, and the role of putative trophic factors thought to act on the target cell.